Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Research Article
  • Published:

Brain-derived-neurotrophic-factor (BDNF) stress response in rats bred for learned helplessness

Molecular Psychiatry volume 6, pages 471–474 (2001)Cite this article

Abstract

Stress-induced elevation of glucocorticoids is accompanied by structural changes and neuronal damage in certain brain areas. This includes reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus which can be prevented by chronic electroconvulsive seizures and antidepressant drug treatment. In the last years we have bred two strains of rats, one which reacts with congenital helplessness to stress (cLH), and one which congenitally does not acquire helplessness when stressed (cNLH). After being selectively bred for more than 40 generations these strains have lost their behavioural plasticity including their sensitivity to antidepressant treatment. We show here that in cLH rats, acute immobilization stress does not induce a reduction of BDNF expression in the hippocampus which is observed in Sprague–Dawley and cNLH rats. All animals tested exhibited elevated corticosterone levels when stressed, an indication, that in cLH rats regulation of BDNF expression in the hippocampal formation is uncoupled from corticosterone increase induced through stress. This may explain the lack of adaptive responses in this strain.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Thoenen H . Neurotrophins and neuronal plasticity Science 1995 50: 593–598

    Article  Google Scholar 

  2. Duman RS, Heninger GR, Nestler EJ . A molecular and cellular theory of depression Arch Gen Psychiatry 1997 54: 597–606

    Article  CAS  Google Scholar 

  3. Siuciak JA, Lewis DR, Wiegand SJ, Lindsay RM . Anti-depressant-like effect of brain-derived neurotrophic factor (BDNF) Pharmacol Biochem Behav 1997 56: 131–137

    Article  CAS  Google Scholar 

  4. Nibuja M, Morinobu S, Duman RS . Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments J Neurosci 1995 15: 7539–7547

    Article  Google Scholar 

  5. Henn FA, Edwards E, Muneyyirci J . Animal models of depression Clin Neurosci 1993 1: 152–156

    Google Scholar 

  6. Hofer M, Pagliusi S, Hohn A, Leibrock J, Barde YA . Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain EMBO J 1990 9: 2459–2464

    Article  CAS  Google Scholar 

  7. Angelucci F, Aloe L, Vasquez PJ, Mathe AA . Mapping the differences in the brain concentration of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in an animal model of depression Neuroreport 2000 11: 1369–1373

    Article  CAS  Google Scholar 

  8. McAllister K, Katz LC, Lo DC . Neurotrophins and synaptic plasticity Annu Rev Neurosci 1999 22: 295–318

    Article  CAS  Google Scholar 

  9. Smith MA, Makino S, Kvetnansky R, Post RM . Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus J Neurosci 1995 15: 1768–1777

    Article  CAS  Google Scholar 

  10. Schaaf MJ, Hoetelmans RWM, de Kloet ER, Vreuggdenhil E . Corticosterone regulates expression of BDNF and trkB but not NT-3 and trkC mRNA in the rat hippocampus J Neurosci Res 1997 48: 334–341

    Article  CAS  Google Scholar 

  11. Kant GJ, Mougey EH, Meyerhoff JL . Diurnal variation in neuroendocrine response to stress in rats: plasma ACTH, β-endorphin, β-LPH, corticosterone, prolactin and pituitary cyclic AMP responses Neuroendocrinology 1986 43: 383–390

    Article  CAS  Google Scholar 

  12. Schaaf MJ, de Jong J, de Kloet ER, Vreuggdenhil E . Downregulation of BDNF mRNA and protein in the rat hippocampus by corticosterone Brain Res 1998 813: 112–120

    Article  CAS  Google Scholar 

  13. Holsboer F . The glucocorticoid receptor hypothesis of depression Neuropsychopharmacology 2000 23: 477–499

    Article  CAS  Google Scholar 

  14. Edwards E, King JA, Fray JC . Increased basal activity of the HPA axis and renin-angiotensin system in congenital learned helplessness in rats exposed to stress early in development Int J Dev Neurosci 1999 17: 805–812

    Article  CAS  Google Scholar 

  15. King JA, Edwards E . Early stress and genetic influences on hypothalamic-pituitary-adrenal axis functioning in adulthood Horm Behav 1999 36: 79–85

    Article  CAS  Google Scholar 

  16. Vecsei P . Glucocorticoids: cortisol, cortisone, corticosterone, compound S, and their metabolites. In: Jaffe BM, Behrmann HR (eds) Methods of Hormone Radioimmunoassays Academic Press: New York 1979 767–792

    Google Scholar 

  17. Meier G . Rebound of aldosterone but not of corticosterone after suppression of adrenal function by triamcinolone acetonide in rats Clin Sci 1988 75: 551–557

    Article  CAS  Google Scholar 

Download references

Acknowledgements

FAH is supported by DFG grant HE 2857/2–2. We are grateful to Dr C Suter-Crazzolara for supplying BDNF cDNA and in situ protocol. We also wish to thank Dr R Spanagel for critical revision of the manuscript, Dr B Krumm for help with statistical analysis, S Keck for expert technical assistance and Dr N Gretz and Dr B Kränzlin for providing animal care facilities and valuable advice on breeding.

Author information

Authors and Affiliations

  1. Central Institute of Mental Health, J5, Mannheim, D-68159, Germany

    B Vollmayr, H Faust & F A Henn

  2. Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, Heidelberg, D-69120, Germany

    S Lewicka

Authors
  1. B Vollmayr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H Faust
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Lewicka
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F A Henn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to F A Henn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vollmayr, B., Faust, H., Lewicka, S. et al. Brain-derived-neurotrophic-factor (BDNF) stress response in rats bred for learned helplessness. Mol Psychiatry 6, 471–474 (2001). https://doi.org/10.1038/sj.mp.4000907

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.mp.4000907

Keywords

This article is cited by

Search

Advanced search

Quick links